Exhaled volatolomics profiling facilitates personalized screening for gastric cancer.

Gastric cancer (GC) is one of the most fatal cancers, characterized by non-specific early symptoms and difficulty in detection. However, there are no valid non-invasive screening tools available for GC. Here we establish a non-invasive method that employs exhaled volatolomics and ensemble learning to detect GC. We developed a comprehensive mass spectrometry-based procedure and determined of a wide range of volatolomics from 314 breath samples. The discovery, identification and verification research screened a biomarker panel to distinguish GC from controls. This panel has achieved 0.90 (0.87-0.94, 95%CI) accuracy, with an area under curve (AUC) of 0.92 (0.89-0.94, 95%CI) in discovery cohort and 0.88 (0.83-0.91, 95%CI) accuracy with an AUC of 0.91 (0.87-0.93, 95%CI) in replication cohort, which outperformed traditional serum markers. Single-cell sequencing and gene set enrichment analysis revealed that these exhaled markers originated from aldehyde oxidation and pyruvate metabolism. Our approach advances the design of exhaled analysis for GC detection and holds promise as a non-invasive method to the clinic.

Microbial Disruptions in Inflammatory Bowel Disease: A Comparative Analysis.

Objective: The fecal microbiota was studied in patients with inflammatory bowel disease (IBD), and the characteristics of gut microbiota were compared among patients with different subtypes and stages of IBD, aiming to identify the gut microbiota associated with IBD. Methods: Fecal samples were collected from 41 IBD patients (18 patients with ulcerative colitis [UC] and 23 patients with Crohn's disease [CD]) in the Department of Gastroenterology of East China Hospital, Fudan University between January 2021 and January 2022. In addition, fecal samples were collected from 20 healthy volunteers. The fecal microbiota was subjected to 16S rRNA gene sequencing, followed by bioinformatics analysis. Results: There was significant difference in the fecal microbiota between IBD patients and controls. The abundance and diversity of fecal microbiota in the IBD patients were significantly lower than in controls. The relative abundance of Subdoligranulum, Ruminococcus, Anaerostipes and Lachnospira was reduced markedly in the IBD patients. As compared to controls, the relative abundance of Streptococcus increased dramatically in the UC patients. The relative abundance of Lachnoclostridium, Fusobacterium, Cloacibacillus and Erysipelatoclostridium significantly increased in the CD patients. As compared to CD patients, the relative abundance of Alistipes was reduced markedly in the UC patients; the relative abundance of Faecalibacterium, Roseburia and Haemophilus was reduced dramatically in the CD patients. In addition, significant difference was also noted in the fecal microflora between patients with active IBD and those with IBD in remission period. In active IBD patients, the relative abundance of Roseburia, Coprococcus and Ruminiclostridium was reduced significantly. Conclusion: There is intestinal microbiota imbalance in IBD patients, and the abundance of Roseburia, Coprococcus and Ruminiclostridium is reduced significantly in the active period of IBD, which may be related to the active IBD.

Causal effects from nonalcoholic fatty liver disease on cholelithiasis: A mendelian randomization study.

Background and Aims: Both nonalcoholic fatty liver disease (NAFLD) and cholelithiasis are highly prevalent hepatobiliary diseases with risk of progression into severe outcomes. Considering the close relationship between liver and gallbladder in anatomy and physiology, a potential causal relationship between NAFLD and cholelithiasis has been speculated. Methods: Mendelian randomization (MR) was employed using genome-wide association study (GWAS) summary statistics in Million Veteran Program (MVP) for NAFLD, and statistics in UK biobank for cholelithiasis. Results: Our results demonstrate that NAFLD has a causal effect on cholelithiasis risk (OR, 1.003; 95%CI, 1.000-1.006; p = 0.03). We also performed the sensitivity analysis and heterogeneity test to ensure the accuracy of outcome and avoid the reverse causality. Conclusion: NAFLD should be regarded as a potential pathogenic factor in pathogenesis study of cholelithiasis, and be considered in assessment and treatment of cholelithiasis.

Tracking of trastuzumab resistance in patients with HER2-positive metastatic gastric cancer by CTC liquid biopsy.

This study aimed to utilize circulating tumor cell-DNA (CTC-DNA) from liquid biopsies to monitor trastuzumab resistance in Gastric cancer (GC) and assess the limited response rate in HER2 metastatic gastric cancer. Given the heterogeneity of GC, we established a high-precision CTC detection system that effectively isolates tumor cells with high HER2 expression for downstream analysis. Targeted sequencing of 610 genes was conducted on 20 paired CTC and tissue samples to assess uniformity. A longitudinal analysis of CTC samples was then performed to monitor trastuzumab resistance throughout treatment. Targeted sequencing of the HER2 gene showed strong consistency with fluorescence in situ hybridization data. Detected HER2 Scna was superior in predicting tumor shrinkage and progression. Most patients with innate trastuzumab resistance exhibited elevated HER2 Scna levels during progression. PIK3CA mutations were significantly enriched, and ERBB2/4 gene mutations were predominant in patients with innate trastuzumab resistance. CTC-DNA sequencing provides new insights into gene alterations associated with trastuzumab resistance in HER2 mGC.

Revealing the Sound Transmission Loss Capacities of Sandwich Metamaterials with Re-Entrant Negative Poisson's Ratio Configuration.

Due to the influence of mass law, traditional lightweight sandwich structures have struggled to surpass solid structures in sound insulation performance. To this end, we propose an acoustic metamaterial structure with a sandwich configuration based on the re-entrant negative Poisson's ratio (NPR) structure and systematically investigate its sound transmission loss (STL) performance under incident plane wave conditions. We used the acoustic impedance tube method to experimentally study the sound insulation performance of the re-entrant NPR sandwich structure under free boundary conditions, and then established an acoustic analysis simulation model based on COMSOL Multiphysics software, which verified that the results obtained by the experiment and the numerical simulation were in good agreement. The results show that the sandwich structure exhibits excellent sound transmission loss performance in the studied frequency range (250-4000 Hz), and the overall sound insulation performance exceeds the curve of the mass theorem, basically achieving more than 20 dB when the sandwich thickness is 2 cm. Finally, we conduct parametric studies to establish a correlation between the geometric design of NPR sandwich structures and their sound transmission loss performance. The research shows that the changes of the length of the ribs, the distance from the ribs to the center of the unit, and the length of the upper wall and the lower wall have a significant impact on the sound insulation performance of the re-entrant NPR sandwich structure, while the change of the wall thickness basically will not affect the sound insulation performance of the sandwich structure. This research can provide practical ideas for the engineering application of noise suppression designs of lightweight structures.

Therapeutic Effect of Prolyl Endopeptidase Inhibitor in High-fat Diet-induced Metabolic Dysfunction-associated Fatty Liver Disease.

Background and Aims: Prolyl endopeptidase (PREP) is a serine endopeptidase that participates in many pathological processes including inflammation, oxidative stress, and autophagy. Our previous studies found that PREP knockout exhibited multiple benefits in high-fat diet (HFD) or methionine choline-deficient diet-induced metabolic dysfunction-associated fatty liver disease (MAFLD). However, cumulative studies have suggested that PREP performs complex functions during disease development. Therefore, further understanding the role of PREP in MAFLD development is the foundation of PREP intervention. Methods: In this study, an HFD-induced MAFLD model at different time points (4, 8, 12, and 16 weeks) was used to explore dynamic changes in the PREP proline-glycine-proline (PGP)/N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) system. To explore its potential value in MAFLD treatment, saline, or the PREP inhibitor, KYP-2047, was administered to HFD-induced MAFLD mice from the 10th to 16th weeks. Results: PREP activity and expression were increased in HFD-mice compared with control mice from the 12th week onwards, and increased PREP mainly resulted in the activation of the matrix metalloproteinase 8/9 (MMP8/9)-PREP-PGP axis rather than the thymosin ß4-meprin α/PREP-AcSDKP axis. In addition, KYP-2047 reduced HFD-induced liver injury and oxidative stress, improved lipid metabolism through the suppression of lipogenic genes and the induction of ß-oxidation-related genes, and attenuated hepatic inflammation by decreasing MMP8/9 and PGP. Moreover, KYP2047 restored HFD-induced impaired autophagy and this was verified in HepG2 cells. Conclusions: These findings suggest that increased PREP activity/expression during MAFLD development might be a key factor in the transition from simple steatosis to steatohepatitis, and KYP-2047 might possess therapeutic potential for MAFLD treatment.

Ductular reaction in non-alcoholic fatty liver disease: When Macbeth is perverted.

Non-alcoholic fatty liver disease (NAFLD) or metabolic (dysfunction)-associated fatty liver disease is the leading cause of chronic liver diseases defined as a disease spectrum comprising hepatic steatosis, non-alcoholic steatohepatitis (NASH), liver fibrosis, cirrhosis, and hepatic carcinoma. NASH, characterized by hepatocyte injury, steatosis, inflammation, and fibrosis, is associated with NAFLD prognosis. Ductular reaction (DR) is a common compensatory reaction associated with liver injury, which involves the hepatic progenitor cells (HPCs), hepatic stellate cells, myofibroblasts, inflammatory cells (such as macrophages), and their secreted substances. Recently, several studies have shown that the extent of DR parallels the stage of NASH and fibrosis. This review summarizes previous research on the correlation between DR and NASH, the potential interplay mechanism driving HPC differentiation, and NASH progression.

Prolyl endopeptidase remodels macrophage function as a novel transcriptional coregulator and inhibits fibrosis.

Macrophages are immune cells crucial for host defense and homeostasis maintenance, and their dysregulation is involved in multiple pathological conditions, such as liver fibrosis. The transcriptional regulation in macrophage is indispensable for fine-tuning of macrophage functions, but the details have not been fully elucidated. Prolyl endopeptidase (PREP) is a dipeptidyl peptidase with both proteolytic and non-proteolytic functions. In this study, we found that Prep knockout significantly contributed to transcriptomic alterations in quiescent and M1/M2-polarized bone marrow-derived macrophages (BMDMs), as well as aggravated fibrosis in an experimental nonalcoholic steatohepatitis (NASH) model. Mechanistically, PREP predominantly localized to the macrophage nuclei and functioned as a transcriptional coregulator. Using CUT&Tag and co-immunoprecipitation, we found that PREP was mainly distributed in active cis-regulatory genomic regions and physically interacted with the transcription factor PU.1. Among PREP-regulated downstream genes, genes encoding profibrotic cathepsin B and D were overexpressed in BMDMs and fibrotic liver tissue. Our results indicate that PREP in macrophages functions as a transcriptional coregulator that finely tunes macrophage functions, and plays a protective role against liver fibrosis pathogenesis.

Galanin ameliorates liver inflammation and fibrosis in mice by activating AMPK/ACC signaling and modifying macrophage inflammatory phenotype.

Background and aims: Galanin is a naturally occurring peptide that plays a critical role in regulating inflammation and energy metabolism, with expression in the liver. The exact involvement of galanin in non-alcoholic fatty liver disease and related fibrosis remains controversial. Methods: The effects of subcutaneously administered galanin were studied in mice with non-alcoholic steatohepatitis (NASH) induced by a high-fat and high-cholesterol diet for 8 weeks, and in mice with liver fibrosis induced by CCl4 for 7 weeks. The underlying mechanism was also studied in vitro on murine macrophage cells (J774A.1 and RAW264.7). Results: Galanin reduced inflammation, CD68-positive cell count, MCP-1 level, and mRNA levels of inflammation-related genes in the liver of NASH mice. It also mitigated liver injury and fibrosis caused by CCl4. In vitro, galanin had anti-inflammatory effects on murine macrophages, including reduced phagocytosis and intracellular reactive oxygen species (ROS). Galanin also activated AMP-activated protein kinase (AMPK)/acetyl-CoA carboxylase (ACC) signaling. Conclusion: Galanin ameliorates liver inflammation and fibrosis in mice, potentially by modifying macrophage inflammatory phenotype and activating AMPK/ACC signaling.

New murine model of alcoholic hepatitis in obesity-induced metabolic-associated fatty liver disease.

Metabolic-associated fatty liver disease (MAFLD) and alcoholic hepatitis (AH) are among the most prevalent liver diseases worldwide, and their coexistence is common in clinical practice. However, currently established models of MAFLD-AH coexistence do not fully replicate their pathological characteristics and require sophisticated experimental techniques. Therefore, we aimed to develop an easily replicable model that mimics obesity-induced MAFLD-AH in patients. Our goal was to establish a murine model that replicates MAFLD and AH coexistence, resulting in significant liver injury and inflammation. To this end, we administered a single ethanol gavage dose to ob/ob mice on a chow diet. The administration of a single dose of ethanol led to elevated serum transaminase levels, increased liver steatosis, and apoptosis in ob/ob mice. Furthermore, ethanol binge caused a significant increase in oxidative stress in ob/ob mice, as measured via 4-hydroxynonenal. Importantly, the single dose of ethanol also markedly exacerbated liver neutrophil infiltration and upregulated the hepatic mRNA expression of several chemokines and neutrophil-related proteins, including Cxcl1, Cxcl2, and Lcn2. Whole-liver transcriptomic analysis revealed that ethanol-induced changes in gene expression profile shared similar features with AH and MAFLD. In ob/ob mice, a single dose of ethanol binge caused significant liver injury and neutrophil infiltration. This easy-to-replicate murine model successfully mimics the pathological and clinical features of patients with coexisting MAFLD and AH and closely resembles the transcriptional regulation seen in human disease.

Retrospective Study on the Effect of Adipose-Derived Stem Cells on the Proliferation and Apoptosis of Keloid Fibroblasts Through the Suppression of ITGA2.

BACKGROUND: Keloid is characterized by excessive collagen accumulation and fibroblast growth, which are fibroproliferative disorders of injured skin, causing functional limitations. Studies have shown that adipose-derived stem cells (ADSCs) inhibit the bioactivity and fibrosis of keloid fibroblasts. However, the molecular mechanism of this effect of ADSCs on keloid formation has not been fully elucidated. METHODS: This in vitro study used fibroblasts obtained from keloids. A consensus gene co-expression network was constructed to focus on identifying consensus gene co-expression modules associated with keloid fibroblasts. Differentially expressed genes (DEGs) were identified between keloid fibroblasts and normal dermal fibroblasts. A functional enrichment analysis was also performed with the DAVID database. A weighted gene co-expression network analysis (WGCNA) was used to screen keloid-related modules using the "WGCNA" R package, followed by hub gene selection in modules from the Protein-protein interaction network through the STRING database. Keloid fibroblasts and ADSCs were extracted and cultured. Proliferation and apoptosis were examined using a 5-ethynyl-2-deoxyuridine (Edu) kit and flow cytometry. RESULTS: We identified 302 DEGs overlapping with a consensus analysis of clusters and a differential expression analysis between keloid fibroblasts and normal dermal fibroblasts. Most of these were involved in collagen binding, extracellular matrix organization, and the PI3K-Akt signaling pathway. WGCNA analysis selected a keloid-associated brown module. ITGA2 was identified as a novel marker in hub genes from the PPI network based on the degree and function of collagen modulation. Furthermore, the proliferation ability of keloid fibroblasts cultured in ADSC medium was inhibited while apoptosis was dramatically increased. Overexpression of ITGA2 reversed the decrease in ADSC-induced apoptosis and increased ADSC-reduced proliferation. CONCLUSION: Our study demonstrated that activation of ITGA2 plays a crucial role in ADSC-induced keloid fibroblast apoptosis and anti-proliferation effects. These results also improved our understanding of the molecular mechanism of the pathogenesis of keloid in response to ADSCs and may contribute to the further development of keloid therapy.

Anti-Aging Effect of the Stromal Vascular Fraction/Adipose-Derived Stem Cells in a Mouse Model of Skin Aging Induced by UVB Irradiation.

Adipose-derived stem cells(ADSCs) have been used for anti-photo-aging. But the purification of ADSCs requires in vitro amplification and culture, there is considerable risk of direct treatment for patients. Stromal vascular fraction(SVF) is a biologically and clinically interesting heterogeneous cell population contains ADSCs. There are few reports on anti-aging effects of SVF in photo-aging skin. The present study investigated the anti-aging effect of stromal vascular fraction (SVF) and adipose-derived stem cells (ADSCs) injection in photo-aging skin. The relationship between the dosage of injection and effect was also discussed. Thirty healthy, 6-week-old, nude rats were randomly divided into the control and experimental groups. The experimental group needing ultraviolet B (UVB) irradiation five days per week, and a duration of 8 weeks. According to different dose regimens of SVF and ADSCs, experiment rats were randomly grouped as the model control group, low-dose (LD) treatment group, middle-dose (MD) treatment group and high-dose (HD) treatment group. At 7 and 28 days post-treatment, specimens were harvested for histological and immunohistochemical analysis. We found that certain concentrations of cells (MD and HD groups) could improve the texture of photoaged skin. Changes in the epidermal cell layer were clearly observed after 7 days of treatment. The epidermal layer becomes thinner and more tender. After 28 days of treatment, the dermal tissue was thickened and the collagen content and proportion were improved. All these indicators showed no significant difference between the same dosages in the two treatment groups. Our results demonstrate that SVF may have anti-aging potential in photo-aging skin and the ADSCs play an important role in SVF. SVF maybe a potential agent for photo-anging skin and the most effective dose of SVF was 106 cells /100 µl/injection point. The proper injection interval may be 1.5 cm.

Prolyl Endopeptidase Gene Disruption Improves Gut Dysbiosis and Non-alcoholic Fatty Liver Disease in Mice Induced by a High-Fat Diet.

The gut-liver axis is increasingly recognized as being involved in the pathogenesis and progression of non-alcoholic fatty liver disease (NAFLD). Prolyl endopeptidase (PREP) plays a role in gut metabolic homeostasis and neurodegenerative diseases. We investigated the role of PREP disruption in the crosstalk between gut flora and hepatic steatosis or inflammation in mice with NAFLD. Wild-type mice (WT) and PREP gene knocked mice (PREPgt) were fed a low-fat diet (LFD) or high-fat diet (HFD) for 16 or 24 weeks. Murine gut microbiota profiles were generated at 16 or 24 weeks. Liver lipogenesis-associated molecules and their upstream mediators, AMP-activated protein kinase (AMPK) and sirtuin1 (SIRT1), were detected using RT-PCR or western blot in all mice. Inflammatory triggers and mediators from the gut or infiltrated inflammatory cells and signal mediators, such as p-ERK and p-p65, were determined. We found that PREP disruption modulated microbiota composition and altered the abundance of several beneficial bacteria such as the butyrate-producing bacteria in mice fed a HFD for 16 or 24 weeks. The level of butyrate in HFD-PREPgt mice significantly increased compared with that of the HFD-WT mice at 16 weeks. Interestingly, PREP disruption inhibited p-ERK and p-p65 and reduced the levels of proinflammatory cytokines in response to endotoxin and proline-glycine-proline, which guided macrophage/neutrophil infiltration in mice fed a HFD for 24 weeks. However, at 16 weeks, PREP disruption, other than regulating hepatic inflammation, displayed improved liver lipogenesis and AMPK/SIRT1 signaling. PREP disruption may target multiple hepatic mechanisms related to the liver, gut, and microbiota, displaying a dynamic role in hepatic steatosis and inflammation during NAFLD. PREP might serve as a therapeutic target for NAFLD.

ZEB1-induced LINC01559 expedites cell proliferation, migration and EMT process in gastric cancer through recruiting IGF2BP2 to stabilize ZEB1 expression.

Gastric cancer (GC) is a common type of tumor that is characterized with high metastatic rate. In recent years, increasing studies have indicated that lncRNAs are involved in the regulation on cancer cell proliferation and migration. However, the functional role of long intergenic non-protein coding RNA 1559 (LINC01559) in GC is still unclear. In this study, we applied quantitative real-time polymerase chain reaction (RT-qPCR) and examined that LINC01559 expression was significantly enhanced in GC cells. Functional assays such as EdU, colony formation, JC-1 and transwell assays displayed that silencing LINC01559 inhibited cell proliferation and migration while promoted cell apoptosis in GC. Besides, western blot analysis and immunofluorescence assays examined the expression of factors related to epithelial-mesenchymal transition (EMT) and indicated that EMT process was blocked by LINC01559 knockdown in GC cells. Besides, LINC01559 silencing inhibited tumor growth in vivo. In addition, Chromatin immunoprecipitation (ChIP) assays demonstrated that zinc finger E-box binding homeobox 1 (ZEB1) served as a transcription factor to combine with LINC01559 promoter and activated the expression of LINC01559 in GC cells. In return, LINC01559 recruited insulin like growth factor 2 mRNA binding protein 2 (IGF2BP2) to stabilize ZEB1 mRNA to up-regulate ZEB1 in GC cells. In short, the findings in this research might provide a novel target for GC treatment.

Prolyl endopeptidase disruption reduces hepatic inflammation and oxidative stress in methionine-choline-deficient diet-induced steatohepatitis.

AIMS: Prolyl endopeptidase (PREP) is a serine endopeptidase widely distributed in the body, and accumulated evidence suggests that PREP participates in inflammation and oxidative stress. Here, we explored the effect of PREP gene disruption on hepatic inflammation and oxidative stress status in a methionine-choline-deficient (MCD)-induced nonalcoholic steatohepatitis (NASH) model. MAIN METHODS: PREP gene disruption (PREPgt) mice and wild-type (WT) littermates were placed on a control or an MCD diet for 4 weeks, respectively. The liver histopathological analysis and the number of inflammatory cells were determined by hematoxylin-eosin (HE) and immunohistochemical staining. Inflammation-associated genes and cytokine levels in liver tissue were evaluated by quantitative PCR and ELISA. The levels of P53, Sesn2, Nrf2, HO-1, and oxidative stress indicators in mice and the palmitic acid (PA)-treated human hepatocellular carcinoma cells (HepG2) were examined by immunoblotting and commercially available kits, respectively. KEY FINDINGS: We found that PREP expression was upregulated in the MCD-induced NASH model. In addition, PREP disruption alleviated MCD-induced hepatic inflammation accompanied by diminished infiltration of inflammatory cells and secretion of inflammatory mediators. More importantly, the results of this study indicate that targeting PREP can improve oxidative stress status in the liver of MCD-diet mice and PA-exposed HepG2 cells. The effect is most likely mediated by the activation of P53 and its downstream signaling pathways (Sesn2/Nrf2/HO-1). SIGNIFICANCE: Our results showed that PREP disruption (or inhibition) could decrease oxidative stress and inflammation and improve liver function, indicating that targeting PREP might be a new potential therapeutic option for NAFLD/NASH.

MSC-induced lncRNA AGAP2-AS1 promotes stemness and trastuzumab resistance through regulating CPT1 expression and fatty acid oxidation in breast cancer.

Trastuzumab resistance has been becoming a major obstacle for treatment of HER-2-positive breast cancer patients. Increasing evidence suggests that mesenchymal stem cells (MSCs) play critical roles during the formation of drug resistance, however, the underlying mechanism is not well known. In this study, mass spectrometry, RNA pulldown and RNA immunoprecipitation assays were performed to verify the direct interactions among AGAP2-AS1 and other associated targets, such as human antigen R (HuR), miR-15a-5p, and carnitine palmitoyl transferase 1 (CPT1). In vitro and in vivo experimental assays were done to clarify the functional role of AGAP2-AS1 in trastuzumab resistance, stemness, and fatty acid oxidation (FAO). The results showed that MSC co-culture induced trastuzumab resistance. AGAP2-AS1 was upregulated in MSC-cultured cells, and knockdown of AGAP2-AS1 reversed the MSC-mediated trastuzumab resistance. Furthermore, MSC culture-induced AGAP2-AS1 regulates stemness and trastuzumab resistance via activating FAO. Mechanistically, AGAP2-AS1 is associated with HuR, and the AGAP2-AS1-HuR complex could directly bind to the CPT1, increasing its expression via improving RNA stability. In addition, AGAP2-AS1 could serve as ceRNA via sponging miR-15a-5p and releasing CPT1 mRNA. Clinically, increased expression of serum AGAP2-AS1 predicts poor response to trastuzumab treatment in breast cancer patients. In conclusion, MSC culture-induced AGAP2-AS1 caused stemness and trastuzumab resistance via promoting CPT1 expression and inducing FAO. Our results provide new insight of the role of MSCs in trastuzumab resistance and AGAP2-AS1 could be promising predictive biomarker and therapeutic target for HER-2+ breast cancer patients.

HOTAIR contributes to the carcinogenesis of gastric cancer via modulating cellular and exosomal miRNAs level.

Gastric cancer (GC) is one of the most leading malignancies. Long noncoding RNA is related to GC. In this study, 11 miRNAs in the exosomes and six lncRNAs in the tissues was examined by qRT-PCR. Correlation analysis was used to analyze the relationship between miRNAs in exosome and lncRNAs in the tissues. Four miRNAs level in GC tissues were examined by qRT-PCR. MTT was used to determine cell viability. Flow cytometry was used to quantify the apoptotic cells. Transwell assay was used to examine the migration and invasion capacity. Dual-luciferase assay was used to examine the interaction between HOTAIR and miR-30a or -b. Capillary formation was used to determine the capillary formation capacity. Weak negative correlations were found between HOTAIR and miR-30a or -b in GC tissue samples. Interestingly, strong negative correlations were identified between the HOTAIR level in GC tissue samples and the miR-30a or -b levels in plasma exosomes. HOTAIR knockdown GC cells exhibited decreased migration, invasion, proliferation, and upregulated apoptosis, which released more miR-30a and -b into the exosomes. KRAS was upregulated when co-cultured with exosomes from HOTAIR overexpressed cells, and promoted GC cells proliferation, migration, and invasion. Meanwhile, HUVEC cells expressed increased VEGF-A and formatted more capillaries. Subsequently, we identified a 10mer target site of miR-30a or -b in HOTAIR sequence, and the overexpression of HOTAIR induced the degradation of miR-30a or -b, indicating a ceRNA role of HOTAIR. We report the negative correlation between the plasma miRNAs level and GC tissue HOTAIR expression for the first time and unveiled the ceRNA role of HOTAIR in GC. HOTAIR functions as an onco-lncRNA regulating the level of miR-30a and -b in both GC cells and exosomes. These findings may give insight into understanding the mechanism of GC pathogenesis and provide new biomarkers for clinical diagnosis.